Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism

Endocrine Journal

Asako Ito¹  Chikara Kagawa¹  Yutaka Mizuno¹  Yatsuka Hibi¹  Masahiro Shibata¹  Katsumi Iwase¹  Fukushi Kambe³  Kimio Ogawa¹  Yoshimi Shimizu¹  Tsuneo Imai² 

[1] Department of Endocrine Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan;Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya 466-8560, Japan;Department of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan

关键词: Parathyroid adenoma;    Primary hyperparathyroidism;    Protein kinase A regulatory subunit type Iα (PRKAR1α);   

DOI  :  10.1507/endocrj.EJ12-0267

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(38)Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity.We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism.The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia.Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed.Western blot and immunohistochemical analyses were employed to evaluate RIα expression.PKA activities were determined in several adenomas highly expressing RIα.RIα expression was also separately evaluated in chief and oxyphilic cells using the “Allred score” system.Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined.Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands.PKA activity in adenomas was significantly less than in normal glands.Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas.In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells.The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.

【 授权许可】

Unknown